This project proposes to identify large (> 50 kDa) surface proteins that are expressed during lung infection by the plague bacterium Yersinia pestis. These will be prioritized by conditions for expression, relative abundance, recognition by plague convalescent serum, and indications from homology with the databases of potential virulence function. Ten of these will be characterized for their necessity for virulence in a mouse model of pneumonic plague, amount that is surface-exposed, and their effects on adherence to a mouse alveolar macrophage cell line and to mouse lung explants. Four will then be chosen for detailed studies of immunogenicity and ability to protect against pneumonic plague. It is hoped that one or more of these will prove to be protective immunogens against pneumonic plague caused by a non-encapsulated strain against which vaccines currently in development will not protect adequately. Such vaccine candidates also will generate a protective immune globulin reagent for rapid protection of potentially exposed people, and a strong, specific antibody reagent might contribute to an improved multiplex detection method. Our findings will enhance our arsenal of means to protect against potential bioterrorism use of Yersinia pestis and also will improve our understanding of the pathogenesis of pneumonic plague.